Recently, a novel mutation, R1135H, in KCNH2, the gene encoding the α-subunit of the rapid delayed rectifier K + channel (I Kr ), has been identified in a patient with short QT interval as well as Brugada-type ECG. Voltage clamp experiments revealed larger tail currents and slowed deactivation of mutant I Kr channels. We have carried out computer simulations to test the effects of the R1135H mutation on the action potential of human left and right ventricular myocytes. Our results demonstrate that this ‘gain-of-function’ mutation in KCNH2 shortens the action potential and enhances the susceptibility of right ventricular myocytes to all-or-none repolarization (epicardial loss of the action potential dome). Thus, the mutation induced changes in I Kr cannot only explain the short QT interval but also the Brugada-type ECG of the patient.